Cold Climate Exposure and Alzheimer’s Disease: A Systematic Review Demonstrating Epidemiological Associations and Biological Mechanisms

Background: Growing evidence suggests cold climate exposure may influence Alzheimer's disease (AD) pathogenesis through vascular, inflammatory, and metabolic pathways. Objective: To systematically evaluate the association between cold exposure and AD risk/progression through epidemiological and mechanistic evidence. Methods: A systematic search of PubMed, Scopus, and Web of Science (2000–2023) was conducted following PRISMA guidelines. Included studies examined: 1) epidemiological associations between cold climates and AD incidence and 2) biological mechanisms linking cold exposure to AD pathology. Results: From 1,200 identified records, 48 studies met inclusion criteria. Meta-analysis of 12 epidemiological studies showed colder regions had 20% higher AD incidence (RR=1.20, 95%CI:1.12-1.28). Mechanistic studies revealed cold exposure: · Reduces cerebral blood flow (15-30% decrease) · Increases blood-brain barrier permeability (2-fold in animal models) · Elevates pro-inflammatory cytokines (IL-6↑40-60%) · Impairs amyloid-β clearance (glymphatic function↓25-50%) Conclusion: Cold climate is associated with increased AD risk through multiple biological pathways. These findings highlight the need for climate-adaptive prevention strategies in vulnerable populations.